CN114341139A - 医用手套用抗微生物盐 - Google Patents
医用手套用抗微生物盐 Download PDFInfo
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- CN114341139A CN114341139A CN202080048592.8A CN202080048592A CN114341139A CN 114341139 A CN114341139 A CN 114341139A CN 202080048592 A CN202080048592 A CN 202080048592A CN 114341139 A CN114341139 A CN 114341139A
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- Prior art keywords
- solvent
- phthalocyanine
- pyridinium
- ion exchange
- iodide
- Prior art date
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- 150000003839 salts Chemical class 0.000 title claims description 5
- 230000000845 anti-microbial effect Effects 0.000 title description 8
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 238000005342 ion exchange Methods 0.000 claims abstract description 10
- 239000012022 methylating agents Substances 0.000 claims abstract description 5
- 125000000129 anionic group Chemical group 0.000 claims abstract description 4
- -1 anionic halide Chemical class 0.000 claims description 17
- 230000008569 process Effects 0.000 claims description 17
- 238000005804 alkylation reaction Methods 0.000 claims description 11
- 239000012296 anti-solvent Substances 0.000 claims description 11
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 claims description 11
- 230000029936 alkylation Effects 0.000 claims description 9
- 239000002168 alkylating agent Substances 0.000 claims description 8
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003849 aromatic solvent Substances 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 239000003456 ion exchange resin Substances 0.000 claims description 3
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 2
- 229940006461 iodide ion Drugs 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 2
- 238000007126 N-alkylation reaction Methods 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- 239000002798 polar solvent Substances 0.000 claims 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 229910052725 zinc Inorganic materials 0.000 description 8
- 239000011701 zinc Substances 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 229910052782 aluminium Inorganic materials 0.000 description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 239000004599 antimicrobial Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 125000000962 organic group Chemical group 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- UMXWTWTZJKLUKQ-UHFFFAOYSA-M lithium;iodide;trihydrate Chemical compound [Li+].O.O.O.[I-] UMXWTWTZJKLUKQ-UHFFFAOYSA-M 0.000 description 4
- XQZYPMVTSDWCCE-UHFFFAOYSA-N phthalonitrile Chemical class N#CC1=CC=CC=C1C#N XQZYPMVTSDWCCE-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000010936 titanium Substances 0.000 description 3
- 229910052719 titanium Inorganic materials 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- CCTDQTKTUQTKFP-UHFFFAOYSA-O 1-ethylpyridin-1-ium-3-ol Chemical compound CC[N+]1=CC=CC(O)=C1 CCTDQTKTUQTKFP-UHFFFAOYSA-O 0.000 description 2
- FZVAZYLFYPULKX-UHFFFAOYSA-O 1-methylpyridin-1-ium-3-ol Chemical compound C[N+]1=CC=CC(O)=C1 FZVAZYLFYPULKX-UHFFFAOYSA-O 0.000 description 2
- BCBDKCSGRVDZMK-UHFFFAOYSA-O 1-propylpyridin-1-ium-3-ol Chemical compound CCC[N+]1=CC=CC(O)=C1 BCBDKCSGRVDZMK-UHFFFAOYSA-O 0.000 description 2
- YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-ethylhexan-1-ol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 229920006391 phthalonitrile polymer Polymers 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 231100000167 toxic agent Toxicity 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- DLGYNVMUCSTYDQ-UHFFFAOYSA-N azane;pyridine Chemical compound N.C1=CC=NC=C1 DLGYNVMUCSTYDQ-UHFFFAOYSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000010961 commercial manufacture process Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Chemical group 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 231100000003 human carcinogen Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000012994 industrial processing Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- BJDYCCHRZIFCGN-UHFFFAOYSA-N pyridin-1-ium;iodide Chemical compound I.C1=CC=NC=C1 BJDYCCHRZIFCGN-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
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- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 150000003752 zinc compounds Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/32—Cationic phthalocyanine dyes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/06—Preparation from carboxylic acids or derivatives thereof, e.g. anhydrides, amides, mononitriles, phthalimide, o-cyanobenzamide
- C09B47/067—Preparation from carboxylic acids or derivatives thereof, e.g. anhydrides, amides, mononitriles, phthalimide, o-cyanobenzamide from phthalodinitriles naphthalenedinitriles, aromatic dinitriles prepared in situ, hydrogenated phthalodinitrile
- C09B47/0675—Preparation from carboxylic acids or derivatives thereof, e.g. anhydrides, amides, mononitriles, phthalimide, o-cyanobenzamide from phthalodinitriles naphthalenedinitriles, aromatic dinitriles prepared in situ, hydrogenated phthalodinitrile having oxygen or sulfur linked directly to the skeleton
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/08—Preparation from other phthalocyanine compounds, e.g. cobaltphthalocyanineamine complex
- C09B47/18—Obtaining compounds having oxygen atoms directly bound to the phthalocyanine skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyridine Compounds (AREA)
Abstract
一种制造酞菁吡啶鎓盐的方法,其中所述方法包括:(a)使酞菁吡啶鎓与甲基化剂反应,以及(b)与阴离子反离子进行离子交换。
Description
技术领域
本发明涉及制造酞菁吡啶鎓盐的方法、可通过本发明方法获得的酞菁吡啶鎓盐、包含酞菁吡啶鎓盐的抗微生物手套的制造以及可通过所述方法获得的抗微生物手套。
背景技术
防护手套广泛应用于医院、制药厂、食品厂、厨房或甚至公共场所。手套通常由聚合物树脂制成。例如,通过使用聚氯乙烯(PVC)作为主要成分来生产所谓的乙烯基手套。常规地,保护手套的使用将细菌与使用者的手隔离开,以降低细菌感染的风险。由于附着在手套表面的细菌没有被杀死,细菌或其他微生物可能会在手套表面生长。因此,手套可能成为新的感染源。
已知单线态氧发生剂破坏微生物。单线态氧比基态、三线态氧具有更大的能量。氧的单线态和三线态通过单线态具有两个反平行自旋的电子和三线态具有平行自旋的非耦合的电子对来区分。单线态氧不同于三线态氧,还因为它是一种活性很高的物质,寿命为数微秒到数百微秒不等。在其寿命期间,单线态氧具有在失活之前发生反应的潜力,因此具有广泛的应用,例如医用手套。
不管制造方法如何,常用的单线态氧发生剂仍然存在溶解性、聚集性、单线态氧产生效率、总体令人不满意的抗微生物活性和稳定性的问题。根据抗微生物剂,其制造过程可能使用有毒试剂。
因此,需要克服这些问题,并优化合成的容易性和安全性、产品保质期、有效且高效的抗微生物活性以及使用者的安全性。
发明内容
本发明提供了一种制备酞菁吡啶鎓盐的方法,其中所述方法包括:
(a)使酞菁吡啶鎓与烷基化剂反应,以及
(b)与阴离子反离子进行离子交换。
具体实施方式
本发明提供了一种制备可用于产生单线态氧的多取代酞菁化合物的方法。酞菁核可以是铝、钛或锌。如果使用铝或钛,铝可以进一步被烷基、芳基、烷氧基、羟基、氧或卤素取代。
选择铝和锌是因为它们比其他金属(例如,铜或镍)更有效地产生单线态氧,并且与其他金属相反,它们相当小,因此可以容易地插入酞菁中,反应在空气中进行(例如使用SiCl4),产率良好,并且易于大量获得。中心金属原子也影响酞菁的吸收最大值的位置,并且锌和铝在化合物中是优选的,因为它们的吸收在光谱的可见光区域中,特别是在600-700nm之间。本文描述的锌化合物是特别优选的。
对于本发明的酞菁,通过氧连接到酞菁核的每个作为侧基的有机基团独立地选自N-烷基化吡啶鎓或吡啶鎓,使得任何一个酞菁核可以携带两个或多个不同的有机基团。N-烷基化吡啶的示例是3-羟基-1-甲基吡啶-1-鎓、3-羟基-1-乙基吡啶-1-鎓、3-羟基-1-丙基吡啶-1-鎓。
此外,本发明中使用的酞菁优选地在与酞菁核相邻的α位(例如化学式1中的1、5、12和13位)具有酞菁核的取代基。这种α取代减少了酞菁的聚集。已知聚集会降低单线态氧的生成效率,因此这种结构防止聚集并提高单线态氧的生成效率,从而提高抗微生物活性和其他活性。为了证明这一点,将酞菁I(参见下面的实施例1)与其中氧基吡啶鎓残基在β位(化学式1中的3、6、11和14位)连接到酞菁核上的类似物进行比较。各将25mg溶解在1L水中,并比较UV/vis吸收。在下面的光谱中可以看出,与聚集的酞菁(这里约640m)相比,α取代方式导致单体酞菁(这里约675nm)的数量比有利于聚集的(这里约635nm)β取代的情况高得多。
因此,相对于β取代方式,α取代的这种使用是新颖的和具有创造性的。
此外,经过广泛的研究,本发明人已经认识到本文所述的分子具有其他期望的特性。它们比市售的类似物(例如Tinolux BBS和Tinolux BMC)更热稳定,对自由基降解更稳定。
根据本发明的酞菁具有以下化学式的结构:
R=R′(a)或R″(b)
R′氧连接的吡啶基
R″氧连接的N-烷基化吡啶鎓
其中:
M选自铝、钛或锌,
R”通过氧原子连接到吡啶基团上,其中至少1个带有阳离子电荷,其余的外围碳原子是未取代的有机基团,
a+b=4
b=1至4
X=Cl-、Br-、I-、甲烷磺酸根、乙烷磺酸根、甲酸根、醋酸根或其它无机的或有机的反离子或其混合物;
并且
其中吡啶氮上的烷基化是任选支化的C1-C8烷基,
酞菁也可以具有以下化学式:
最优选的是具有以下化学式的四吡啶氧基酞菁锌:
其中烷基化吡啶的中位平均总数为2-4,优选3-4。由于这种盐的溶解性和物理特性,优选的反离子“X”是碘离子。
对于本发明的酞菁,通过氧连接到酞菁核的每个作为侧基的有机基团独立地选自N-烷基化吡啶鎓或吡啶鎓,使得任何一个酞菁核可以携带两个或多个不同的有机基团。N-烷基化吡啶的示例是3-羟基-1-甲基吡啶-1-鎓、3-羟基-1-乙基吡啶-1-鎓、3-羟基-1-丙基吡啶-1-鎓。
在这种酞菁的优选的基团中,阳离子取代基的总数为2-4,更优选为3-4。本文所述的化合物可以具有至少+1,最高+4,优选+2至+4,最优选+3至+4的电荷。适用于N-烷基化吡啶的反离子包括但不限于碘离子、氯离子、溴离子、甲烷磺酸根、甲苯磺酸根、醋酸根和六氟磷酸根。
本发明中使用的抗微生物剂可以被光活化,并实现从手套上持续释放单线态氧。已知,单线态氧是杀死大多数细菌的一种强力抗菌剂。产生单线态氧的染料的优点是它们是催化的,不会随时间耗尽,并且它们释放的单线态氧不是持久的,因为所述单线态氧的半衰期非常短,通常为数微秒。这在毒性和开发耐药菌的潜力方面具有主要优势。
化学式1的酞菁可以通过以下来制备:
(1)与(2)反应,
(1)化学式2的取代的1,2-二氰基苯:
其中Z选自氯基、溴基和碘基或硝基,并且位于其中一个CN基团的3位(α),
(2)吡啶-OH化合物,
其中基团Z被吡啶-O基团取代,以形成化学式(3)的化合物
然后,可以使一种或多种化学式3的1,2-二氰基苯化合物、或一种或多种化学式3的化合物和1,2-二氰基苯的组合,与合适的金属或金属盐任选地在惰性液体中在高温下反应以形成化学式1的酞菁。
在GB 1489394、GB 2200650和DE 2455675中充分描述了这样的反应。
在制造过程中,吡啶基团的烷基化最后进行。如果该过程没有完成,一些吡啶取代基可以保持未烷基化和不带电。该方法可以通过温度和化学计量来改进,以得到更高或更低的最终烷基化程度。
然而,这样的烷基化步骤可能使用有毒试剂。硫酸二甲酯是一种人类致癌物,因其毒性而被列入ECHA(欧洲化学品管理局)的“高度关注的物质”名单。此外,硫酸二甲酯不会返回所需的卤离子,例如碘离子,反离子。碘甲烷会提供合适的反离子,但作为IARC(国际癌症研究机构,世界卫生组织的一部分)2类致癌物具有毒性问题。此外,碘甲烷是高挥发性的,其需要昂贵的工程控制来进行工业处理和控制。
因此,本发明还提供了避免使用这样的有毒试剂的替代的制造方法,其中用烷基化剂例如磺酸酯或碳酸酯,优选甲基化剂,最优选对甲苯磺酸甲酯进行烷基化。这种试剂没有报道的致癌风险,并且具有低蒸气压,其可以作为易于处理的液体在工业上使用。首先形成的酞菁吡啶鎓甲苯磺酸盐作为粘性树脂给出了不可接受的物理形式。例如,在酞菁吡啶鎓碘化物的情况下,本发明认识到反离子交换可以通过用碘化物盐溶液或碘溶液淬灭反应来实现。
使用卤化物(例如碘化物)溶液是本发明的一个优点。对于这样的反离子交换,最通常的是使用离子交换树脂。然而,这样做的缺点是需要形成难溶性产品的稀溶液,并且使用昂贵的树脂,该树脂不容易以碘化物的形式在市场上获得。因此,在商业制造中,要求使用稀释溶液和树脂是非常低效的。
此外,在本发明的方法中,其中可以使中间体吡啶基酞菁与磺酸酯或碳酸酯,优选对甲苯磺酸甲酯进行烷基化反应,不进行单独的干燥步骤。吡啶基酞菁以本领域技术人员熟知的常规方式由吡啶基邻苯二甲腈环化形成。环化后,用反溶剂沉淀吡啶基酞菁。这样的反溶剂可以是水、酮、酯或芳族溶剂,或者优选醇溶剂,例如甲醇、乙醇或丙醇异构体。吡啶基酞菁“湿滤饼”的干燥可能会很久,显著地影响制造周期时间。本发明进一步认识到“湿滤饼”可以在不进行干燥的情况下直接加入烷基化反应介质中。本发明还发现烷基化反应可以成功进行,特别是如果首先通过蒸馏除去过量的反溶剂。然后可以加入甲基化试剂,例如磺酸酯或碳酸酯,优选对甲苯磺酸甲酯,烷基化反应继续进行,得到酞菁吡啶鎓化合物(例如碘化物),没有影响。本发明减少了制造周期时间并显著降低了成本。
通过本发明的方法制造的抗微生物剂可用于涂覆医用手套,其可提供有效且持续的抗微生物保护。此外,不明显降低手套的物理特性。
虽然已经根据目前被认为是最实用和优选的实施方案描述了本发明,但是应当理解,本发明不必局限于所公开的实施方案。相反,它旨在覆盖包括在所附权利要求书范围内的各种改进和类似配置,权利要求书符合最宽泛的解释,从而涵盖所有这样的改进和类似结构。
本发明将通过参考以下实施例但不以限制的方式来说明本发明。
实施例
实施例1-使用对甲苯磺酸甲酯和碘化锂由吡啶基酞菁II制备酞菁吡啶鎓碘化物I
向NMP(360g)中加入吡啶基酞菁锌II(140g,1当量,0.147mol)和对甲苯磺酸甲酯(120g,0.644mol,4.4当量)。将反应物搅拌并加热至107-111℃(内部容器温度)20小时,然后冷却至50-60℃(内部容器温度)。同时,向第二个容器中加入异丙醇(14个体积份,2000mL)和碘化锂三水(125g=0.668mol=4.54当量)。将反应混合物转移到第二个容器中以沉淀粗产物,通过过滤分离粗产物并用另外的异丙醇洗涤。将粗产物的湿滤饼再次加入具有异丙醇(8个体积份,1100mL)和碘化锂三水(35g,0.187mol,1.27当量)的容器中。将浆液加热至80-83℃(内部容器温度),然后冷却至室温。通过过滤分离最终产物,用另外的异丙醇洗涤,然后在烘箱中干燥。
实施例2–在不干燥中间体的情况下由吡啶基邻苯二甲腈III制备酞菁吡啶鎓碘化物I
向2-乙基己醇(242g)中加入3-(氧基吡啶基)邻苯二甲腈(145g,0.656mol,1当量),并用惰性气体吹扫容器。加入氯化锌(21g,0.154mol,理论电荷的94%),然后加入DBU(51g,0.335mol,0.51当量)。将反应加热至约107℃(内部容器温度)至少16小时。冷却反应,向反应混合物中加入异丙醇(1600mL)。冷却至室温后,通过过滤分离吡啶基酞菁锌II,并用另外的异丙醇洗涤。将粗制的湿滤饼吡啶基锌酞菁II加入NMP(360克)并加热至80℃。通过减压蒸馏除去湿滤饼中携带的溶剂。接着加入对甲苯磺酸甲酯(120g=0.644mol=4.4当量)。将反应搅拌并加热至107-111℃(内部容器温度)20小时,然后冷却至50-60℃(内部容器温度)。同时,向第二个容器中加入异丙醇(14个体积份,2000mL)和碘化锂三水(125g=0.668mol=4.54当量)。将反应混合物转移到第二个容器中以沉淀粗产物,通过过滤分离粗产物并用另外的异丙醇洗涤。将粗产物的湿滤饼再次加入具有异丙醇(8个体积份,1100mL)和碘化锂三水(35g,0.187mol,1.27当量)的容器中。将浆液加热至80-83℃(内部容器温度),然后冷却至室温。通过过滤分离最终产物,用另外的异丙醇洗涤,然后在烘箱中干燥。
实施例3-带有对甲苯磺酸根反离子的酞菁吡啶鎓的制备
向NMP(18.10g)中加入吡啶基酞菁锌II(7.25g,1当量,0.0076mol)和对甲苯磺酸甲酯(6.22g,0.0334mol,4.4当量)。将反应搅拌并加热至107-111℃(内部容器温度)20h,然后冷却至50-60℃(内部容器温度)。同时,向第二个容器中加入异丙醇(14个体积份,200mL)。将反应混合物转移到第二个容器中以沉淀粗产物。产物沉淀为粘性物质。当试图通过过滤进行标准分离时,并不是所有的粘性物质都从反应烧瓶中倒出,剩余的保持粘附在内表面上。因此,对甲苯磺酸根(“甲苯磺酸根”)反离子不能使产品具有合适的用于制造的物理特性。
权利要求书(按照条约第19条的修改)
1.一种制造酞菁吡啶鎓盐的方法,其中所述方法包括:
(a)使酞菁吡啶鎓与烷基化剂反应,其中所述烷基化剂上被取代的“离去基团”不是碘离子,以及
(b)随后与阴离子卤化物反离子进行离子交换;
其中通过过滤从反溶剂中分离出中间体吡啶基酞菁,
并且其中所述反溶剂为酮、酯或芳族溶剂或醇,优选丙醇异构体。
2.根据权利要求1所述的制造酞菁吡啶鎓盐的方法,其中所述方法包括:
(a)使酞菁吡啶鎓与对甲苯磺酸甲酯反应,以及
(b)随后与阴离子卤化物反离子进行离子交换,以得到最终产物碘化物盐。
3.根据权利要求1所述的方法,其中所述烷基化剂是甲基化剂,优选磺酸酯或碳酸酯,最优选对甲苯磺酸甲酯。
4.根据前述权利要求中任一项所述的方法,其中最终阴离子抗衡离子是碘离子。
5.根据前述权利要求中任一项所述的方法,其中所述离子交换不使用离子交换树脂。
6.根据前述权利要求中任一项所述的方法,其中所述中间体吡啶基酞菁分离物在不进行单独的干燥步骤的情况下作为湿滤饼在烷基化中使用。
7.根据前述权利要求中任一项所述的方法,其中所述湿滤饼具有0-300重量%,优选0-100重量%,最优选20-60重量%的反溶剂含量。
Claims (14)
1.一种制造酞菁吡啶鎓盐的方法,其中所述方法包括:
(a)使酞菁吡啶鎓与烷基化剂反应,其中所述烷基化剂上被取代的“离去基团”不是碘离子,以及
(b)随后与阴离子卤化物反离子进行离子交换。
2.一种制造酞菁吡啶鎓盐的方法,其中所述方法包括:
(a)使酞菁吡啶鎓与对甲苯磺酸甲酯反应,以及
(b)随后与阴离子卤化物反离子进行离子交换,以得到最终产物碘化物盐。
3.根据权利要求1或2所述的方法,其中所述烷基化剂是甲基化剂,优选磺酸酯或碳酸酯,最优选对甲苯磺酸甲酯。
4.根据前述权利要求中任一项所述的方法,其中最终阴离子抗衡离子是碘离子。
5.根据前述权利要求中任一项所述的方法,其中所述离子交换不使用离子交换树脂。
6.根据前述权利要求中任一项所述的方法,其中通过过滤从反溶剂中分离出中间体吡啶基酞菁。
7.根据权利要求6所述的方法,其中所述中间体吡啶基酞菁分离物在不进行单独的干燥步骤的情况下作为湿滤饼在烷基化中使用。
8.根据权利要求7所述的方法,其中所述湿滤饼具有0-300重量%,优选0-100重量%,最优选20-60重量%的反溶剂含量。
9.根据权利要求6-8中任一项所述的方法,其中所述反溶剂选自有机溶剂或水。
10.根据权利要求6-9中任一项所述的方法,其中所述反溶剂为酮、酯或醇,其中优选丙醇异构体。
11.根据权利要求6-10中任一项所述的方法,其进一步包括用于烷基化的溶剂,并且其中通过蒸馏除去所述反溶剂。
12.根据权利要求11所述的方法,其中所述溶剂为有机溶剂或水。
13.根据权利要求11或12所述的方法,其中所述溶剂是极性溶剂,优选酯、酰胺、醇或芳族溶剂,更优选偶极非质子溶剂,例如(但不限于)DMF、NMP或DMSO。
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